Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma

Maesaka, Kazuki; Hikita, Hayato; Kai, Machiko; Tahata, Yuki; Shirai, Kumiko; Doi, Akira; Murai, Kazuhiro; Saito, Yoshinobu; Yamada, Ryoko; Kodama, Takahiro; Ohkawa, Kazuyoshi; Miyazaki, Masanori; Ishida, Hisashi; Matsumoto, Kengo; Nozaki, Yasutoshi; Yakushijin, Takayuki; Sakamori, Ryotaro; Tatsumi, Nobuyuki; Iio, Sadaharu; Nawa, Takatoshi; Kakita, Naruyasu; Nakahara, Masanori; Hosui, Atsushi; Usui, Takeo; Imanaka, Kazuho; Doi, Yoshinori; Sakakibara, Mitsuru; Yoshida, Yuichi; Tatsumi, Tomohide; Takehara, Tetsuo

doi:https://doi.org/10.1111/jgh.70068

Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma

Maesaka, Kazuki; Hikita, Hayato; Kai, Machiko et al.

Journal of Gastroenterology and Hepatology (Australia), 2025, 40(10), 2580-2590

アクセス数:36件（2025-12-05 06:38 集計）

固定URL: https://hdl.handle.net/11094/102961

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タイトル	Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma
著者	NRID 1000080974857 1000080974857 ORCID 0009-0007-5642-9470 0009-0007-5642-9470 researchmap permalink maesaka maesaka Scopus Author ID 57205239322 57205239322 著者名 Maesaka, Kazuki
	NRID 1000020623044 1000020623044 ORCID 0000-0003-2488-7315 0000-0003-2488-7315 researchmap permalink hikitahayato hikitahayato Scopus Author ID 23667454900 23667454900 著者名 Hikita, Hayato
	著者名 Kai, Machiko
	NRID 1000000838047 1000000838047 ORCID 0000-0002-9116-7054 0000-0002-9116-7054 researchmap permalink yuki.tahata yuki.tahata Scopus Author ID 56755390400 56755390400 著者名 Tahata, Yuki
	NRID 1000020992267 1000020992267 researchmap permalink u987841f u987841f 著者名 Shirai, Kumiko
	著者名 Doi, Akira
	NRID 1000050867314 1000050867314 ORCID 0000-0001-8634-2922 0000-0001-8634-2922 researchmap permalink murai_kazuhiro murai_kazuhiro Scopus Author ID 57202460806 57202460806 著者名 Murai, Kazuhiro
	NRID 1000060814598 1000060814598 ORCID 0000-0002-0624-0449 0000-0002-0624-0449 researchmap permalink saito_yoshinobu saito_yoshinobu Scopus Author ID 55912459300 55912459300 著者名 Saito, Yoshinobu
	NRID 1000070774339 1000070774339 著者名 Yamada, Ryoko
	NRID 1000010623275 1000010623275 ORCID 0000-0002-6250-1324 0000-0002-6250-1324 researchmap permalink takahirokodama takahirokodama Scopus Author ID 35193885800 35193885800 著者名 Kodama, Takahiro
	NRID 1000080432540 1000080432540 著者名 Ohkawa, Kazuyoshi
	著者名 Miyazaki, Masanori
	著者名 Ishida, Hisashi
	著者名 Matsumoto, Kengo
	著者名 Nozaki, Yasutoshi
	著者名 Yakushijin, Takayuki
	NRID 1000010644685 1000010644685 著者名 Sakamori, Ryotaro
	著者名 Tatsumi, Nobuyuki
	著者名 Iio, Sadaharu
	著者名 Nawa, Takatoshi
	著者名 Kakita, Naruyasu
	著者名 Nakahara, Masanori
	NRID 1000010536882 1000010536882 著者名 Hosui, Atsushi
	著者名 Usui, Takeo
	著者名 Imanaka, Kazuho
	著者名 Doi, Yoshinori
	著者名 Sakakibara, Mitsuru
	著者名 Yoshida, Yuichi
	NRID 1000020397699 1000020397699 researchmap permalink read0140669 read0140669 Scopus Author ID 7202112131 7202112131 著者名 Tatsumi, Tomohide
	NRID 1000070335355 1000070335355 著者名 Takehara, Tetsuo
キーワード等	adverse event
	irAE
	landmark analysis
内容	Maesaka K., Hikita H., Kai M., et al. Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma. Journal of Gastroenterology and Hepatology (Australia) 40(10), 2349 (2025); https://doi.org/10.1111/jgh.70068.
抄録	Background and Aim: Atezolizumab plus bevacizumab is used as a first-line treatment for unresectable hepatocellular carcinoma (uHCC). However, the relationship between its adverse events (AEs) and treatment efficacy remains unclear. In this study, we aimed to clarify this association. Methods: This study included 187 patients with uHCC treated with atezolizumab plus bevacizumab as first-line therapy at 19 affiliated hospitals in the Osaka Liver Forum. A landmark analysis was conducted to address biases in AE incidence. Results: The objective response and disease control rates were 28.2% and 69.6%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 7.4 and 24.6 months, respectively. Among the 187 patients, 178 (95.2%) experienced at least one AE, with proteinuria being the most common (41.7%), followed by hypertension (34.8%) and fatigue (30.5%). All three major AEs had a median onset time of 6 weeks. We set the landmark point at Week 9 after treatment initiation, considering that the onset time for most AEs was within 9 weeks. In the landmark analysis, multivariable analysis identified the absence of bevacizumab interruption within 9 weeks and the occurrence of hypertension within 9 weeks as predictors of prolonged PFS. mALBI Grade 1/2a, the occurrence of hypertension, and the absence of fatigue and rash within 9 weeks were associated with prolonged OS. These results were consistent with those from the 6-week landmark analysis. Conclusions: Patients with hypertension occurring as an AE within 9 weeks are expected to have better PFS and OS with atezolizumab plus bevacizumab therapy for uHCC.
出版者	John Wiley and Sons Inc
収録物名	Journal of Gastroenterology and Hepatology (Australia)
巻(号)	40(10)
ページ	2580-2590
刊行年月	2025-09-09
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102961
PISSN	08159319
eISSN	14401746
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1111/jgh.70068
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
権利情報	© 2025 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Gastroenterology and Hepatology (Australia). 2025, 40(10), p. 2580-2590
DC.title	Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma
DC.creator	Maesaka, Kazuki
	Hikita, Hayato
	Kai, Machiko
	Tahata, Yuki
	Shirai, Kumiko
	Doi, Akira
	Murai, Kazuhiro
	Saito, Yoshinobu
	Yamada, Ryoko
	Kodama, Takahiro
	Ohkawa, Kazuyoshi
	Miyazaki, Masanori
	Ishida, Hisashi
	Matsumoto, Kengo
	Nozaki, Yasutoshi
	Yakushijin, Takayuki
	Sakamori, Ryotaro
	Tatsumi, Nobuyuki
	Iio, Sadaharu
	Nawa, Takatoshi
	Kakita, Naruyasu
	Nakahara, Masanori
	Hosui, Atsushi
	Usui, Takeo
	Imanaka, Kazuho
	Doi, Yoshinori
	Sakakibara, Mitsuru
	Yoshida, Yuichi
	Tatsumi, Tomohide
	Takehara, Tetsuo
DC.publisher	John Wiley and Sons Inc
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-09-09
DC.identifier	https://doi.org/10.1111/jgh.70068
DC.subject	adverse event
	irAE
	landmark analysis
DC.description	Maesaka K., Hikita H., Kai M., et al. Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma. Journal of Gastroenterology and Hepatology (Australia) 40(10), 2349 (2025); https://doi.org/10.1111/jgh.70068.
DCTERMS.abstract	Background and Aim: Atezolizumab plus bevacizumab is used as a first-line treatment for unresectable hepatocellular carcinoma (uHCC). However, the relationship between its adverse events (AEs) and treatment efficacy remains unclear. In this study, we aimed to clarify this association. Methods: This study included 187 patients with uHCC treated with atezolizumab plus bevacizumab as first-line therapy at 19 affiliated hospitals in the Osaka Liver Forum. A landmark analysis was conducted to address biases in AE incidence. Results: The objective response and disease control rates were 28.2% and 69.6%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 7.4 and 24.6 months, respectively. Among the 187 patients, 178 (95.2%) experienced at least one AE, with proteinuria being the most common (41.7%), followed by hypertension (34.8%) and fatigue (30.5%). All three major AEs had a median onset time of 6 weeks. We set the landmark point at Week 9 after treatment initiation, considering that the onset time for most AEs was within 9 weeks. In the landmark analysis, multivariable analysis identified the absence of bevacizumab interruption within 9 weeks and the occurrence of hypertension within 9 weeks as predictors of prolonged PFS. mALBI Grade 1/2a, the occurrence of hypertension, and the absence of fatigue and rash within 9 weeks were associated with prolonged OS. These results were consistent with those from the 6-week landmark analysis. Conclusions: Patients with hypertension occurring as an AE within 9 weeks are expected to have better PFS and OS with atezolizumab plus bevacizumab therapy for uHCC.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.rights	© 2025 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
DC.format	102961
citation_title	Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma
citation_author	Maesaka, Kazuki
	Hikita, Hayato
	Kai, Machiko
	Tahata, Yuki
	Shirai, Kumiko
	Doi, Akira
	Murai, Kazuhiro
	Saito, Yoshinobu
	Yamada, Ryoko
	Kodama, Takahiro
	Ohkawa, Kazuyoshi
	Miyazaki, Masanori
	Ishida, Hisashi
	Matsumoto, Kengo
	Nozaki, Yasutoshi
	Yakushijin, Takayuki
	Sakamori, Ryotaro
	Tatsumi, Nobuyuki
	Iio, Sadaharu
	Nawa, Takatoshi
	Kakita, Naruyasu
	Nakahara, Masanori
	Hosui, Atsushi
	Usui, Takeo
	Imanaka, Kazuho
	Doi, Yoshinori
	Sakakibara, Mitsuru
	Yoshida, Yuichi
	Tatsumi, Tomohide
	Takehara, Tetsuo
citation_publisher	John Wiley and Sons Inc
citation_language	英語
citation_date	2025-09-09
citation_journal_title	Journal of Gastroenterology and Hepatology (Australia)
citation_volume	40
citation_issue	10
citation_firstpage	2580
citation_lastpage	2590
citation_doi	https://doi.org/10.1111/jgh.70068
citation_public_url	https://hdl.handle.net/11094/102961

Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma

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